Binuclear Copper(II) Complexes Modified with Pyrene: DNA

Binuclear Copper(II) Complexes Modified with Pyrene: DNA Cleavage and
Binding Properties
Saibert1*, C., da Silva2, M. P., Neves2, A., Terenzi1, H.
1
Centro de Biologia Molecular Estrutural, Departamento de Bioquímica,
Universidade Federal de Santa Catarina, Santa Catarina, Brazil.
2
Departamento de Química, Universidade Federal de Santa Catarina, Santa
Catarina, Brazil.
Introduction: in the last years, binuclear complexes of copper(II) have gained
attention because of the large activity as DNA cleavage agents. We report here
two new binuclear copper(II) complexes, derived from the Cu2(L-TCl) (1), that
present strong DNA cleavage properties: Cu2(L-Tdab) (2) and Cu2(L-TN-Mepydab)
(3), where L-TCl is 2-chloro-4,6-bis(di-2-picolylamino)-1,3,5-triazine; L-Tdab is 2diaminobutane-4,6-bis(di-2-picolylamino)-1,3,5-triazine and L-TN-Mepydab is 2-Nmethylpyrenyldiaminobutane-4,6-bis(di-2-picolylamino)-1,3,5-triazine.
Objectives: compare the activity of the complexes 2 and 3 towards 1,
searching for structure-activity relationships, especially for the pyrene-derived
complex (3) since pyrene is a well know intercalating agent. Material and
methods: the ability of title complexes to cleave DNA was examined following
the conversion of supercoiled form of pBSK-II plasmid into its cleaved forms
using agarose gel. Similarly the cleavage of a fluorescent end-labeled hairpin
DNA by the complexes was investigated using urea page polyacrylamide gel
electrophoresis. Results and discussion: complexes 2 and 3 showed high
activity in terms of plasmid DNA cleavage, even at mild conditions (pH 7.0,
37°C), low concentration and incubation time. The reaction mechanism seems
to be oxidative. The complexes have preference for the minor groove of DNA
and kinetic parameters indicate an enhancement of complex/DNA affinities from
1 to 3, since the KM decreases accordingly. In addition, the rate of the cleavage
reaction (kcat) is likely the same for all. The high resolution gel analysis suggests
that the complexes cleave DNA in the vicinity of a hairpin structure.
Conclusions: the substitution of chlorine by butanodiamine and the posterior
addition of a pyrene moiety increased the affinity of the complexes for DNA,
without changing the rate of cleavage. The high activity of 3 in comparison to 1
and 2 by the addition of pyrene motifs is a good strategy to increase the
cleavage activity of metal complexes without changes in the catalytic
mechanism.
Keywords: DNA cleavage, binuclear copper(II) complexes, pyrene
Financial Support: CNPq, CAPES, MCT, FINEP, FAPESC, INCT - Biologia
Estrutural e Bioimagem.
*Correspondence to: [email protected]; [email protected]